The long-term goal of the research is to better understand the neural control of posture and balance. Adequate control of posture is vital for the performance of functional motor tasks, yet little is understood about the sources of sensory feedback and their integration in balance control. The studies in this proposal focus on the role of somatosensory afferents in balance using a novel model of peripheral sensory neuropathy, in which a high dose of pyridoxine (vitamin B6) is used to induce widespread deafferentation. This approach has the potential to reveal new and significant information about the role of somatosensation in motor control. The role of somatosensory afferents in the control of posture and balance is unclear. Specific aims 1 and 2 will examine the role of somatosensory inputs in: 1) the automatic postural response to unexpected disturbances of stance, 2) the anticipatory postural adjustment that accompanies voluntary movements. Specific aim 3 will determine the temporal sequence and spatial pattern of large fiber deafferentation induced by pyridoxine at both the functional and the morphological levels. Our preliminary data show that the loss of large diameter afferent fibers that is induced by pyridoxine toxicity results in a significant delay of the automatic postural response to sudden movements of the support surface during stance. This observation is very exciting because it may lead to the first clear demonstration that somatosensory inputs are critical for triggering of the early, automatic postural response. Peripheral neuropathy is a significant health problem not only as a result of common syndromes such as diabetes but also as part of the aging process. Clinical neuropathies often have mixed motor and sensory fiber involvement. The loss of either motor or sensory fibers or both could result in ataxia and balance difficulties with the associated risk of falling. The studies in this proposal will provide a clearer understanding of the role of somatosensory afferents in balance and thereby may suggest better diagnostic tools for evaluating the mechanism of a balance disorder in patients with peripheral neuropathy. Further, this understanding may lead to new ideas and rehabilitation techniques for improving balance in these patients.